Malignant plasma cells secrete a number of effector and regulator products among which are immunoglobulin, osteoclast activating factor, interferon, and PC factor. PC factor appears to act upon macrophages, inducing them to secrete a plasmacytoma-induced macrophage substance (PIMS), which suppresses antibody production by antigen-stimulated normal spleen cells. This regulatory loop is responsible for the profound immunosuppression observed in hosts of plasma cell tumors. During the first two years of this funding period, we have succeeded in identifying a number of plasmacytoma cell lines which fail to secrete immunoglobulin but continue to secrete PC-factor. Most experiments are now being conducted with one of these lines, SP-2. We are currently cloning this line and testing the clones to pick a clone that no longer produces PC-factor. Possession of positive and negative clones for PC-factor production will greatly facilitate further studies of the factor. Simultaneously, we have developed an efficient assay for PC-factor, which consists of a proliferation assay rather than the previously used in vitro assay utilizing the Mishell-Dutton technique in disposable diffusion chambers. Development of this proliferation assay was based on findings in a third major area of interest: the effect of plasmacytomas and the factors they produce and induce on B cells. In this third area of concern, we have now shown that suppressor macrophages, induced by PC-factor, inhibit B-cell proliferation via PIMS, the plasmacytoma-induced macrophage substance. Studies recently completed demonstrate that PIMS inhibits B-cell activation by freezing them in the late G1 phase of the cell cycle. These studies constitute the most complete and detailed investigation in the field of the immunoregulatory effects of tumor-derived factors on the immune system. (HF)